Circulating 25-hydroxyvitamin D, VDR polymorphisms, and survival in advanced non-small-cell lung cancer.
OBJECTIVE
We showed previously that in early-stage non-small-cell lung cancer (NSCLC), serum vitamin D levels and VDR polymorphisms were associated with survival. We hypothesized that vitamin D levels and VDR polymorphisms may also affect survival among patients with advanced NSCLC.


METHODS
We evaluated the relationship between circulating 25-hydroxyvitamin D levels; VDR polymorphisms, including Cdx-2 G>A (rs11568820), FokI C>T (rs10735810), and BsmI C>T (rs144410); and overall survival among patients with advanced NSCLC. Analyses of survival outcomes were performed using the log-rank test and Cox proportional hazards models, adjusting for sex, stage, and performance status.


RESULTS
There were 294 patients and 233 deaths, with median follow-up of 42 months. We found no difference in survival by circulating vitamin D level. The C/C genotype of the FokI polymorphism was associated with improved survival: median survival for C/C was 21.4 months, for C/T was 12.1 months, and for T/T was 15.6 months (log-rank P = .005). There were no significant effects on survival by the Cdx-2 or BsMI polymorphism. However, having increasing numbers of protective alleles was associated with improved survival (adjusted hazard ratio for two or more v zero to one protective alleles, 0.57; 95% CI, 0.41 to 0.79; P = .0008). On haplotype analysis, the G-T-C (Cdx-2-FokI-BsmI) haplotype was associated with worse survival compared with the most common haplotype of G-C-T (adjusted hazard ratio, 1.61; 95% CI, 1.21 to 2.14; P = .001).


CONCLUSIONS
There was no main effect of vitamin D level on overall survival in the advanced NSCLC population. The T allele of the VDR FokI>T polymorphism and the G-T-C (Cdx-2-FokI-BsmI) haplotype were associated with worse survival.
Heist
Rebecca Suk
RS
Massachusetts General Hospital, USA.
Zhou
Wei
W
Wang
Zhaoxi
Z
Liu
Geoffrey
G
Neuberg
Donna
D
Su
Li
L
Asomaning
Kofi
K
Hollis
Bruce W
BW
Lynch
Thomas J
TJ
Wain
John C
JC
Giovannucci
Edward
E
Christiani
David C
DC
D000328:Adult; D000368:Aged; D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics* / Q000401:mortality; D005260:Female; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000097:blood* / Q000235:genetics*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
D018167:Receptors, Calcitriol; D014807:Vitamin D; C104450:25-hydroxyvitamin D